Project Abstract We propose to continue a highly successful Training Program in the Molecular Biology of Neurodegeneration and Alzheimer's disease - a program devoted to the training of pre- and postdoctoral students for careers as independent research scientists in universities and health-related research laboratories. The trainers are all Harvard faculty members with active research programs related to neurodegeneration, with an emphasis on Alzheimer's disease and other neurodegenerative disorders related to aging. They are drawn from the Harvard Medical School and six affiliated research hospitals: Beth Israel-Deaconess Medical Center, Brigham and Women's Hospital, Children's Hospital, Dana-Farber Cancer Institute, Massachusetts General Hospital, and McLean Hospital. Bringing a wide range of experience and experimental approaches to the problems of age- related neurodegeneration, the Program faculty includes molecular biologists, geneticists, cell biologists, neuropathologists, and biochemists. The predoctoral students are recruited into and drawn from the graduate students in the degree-granting Neuroscience Program of the Harvard Medical School. The postdoctoral students are chosen from among applicants nominated by individual faculty members of the Program. Selection of trainees occurs through a competitive process mediated by a Training Grant Advisory Committee. A total of six predoctoral trainees and eight postdoctoral trainees are proposed for a primary training faculty of 26 individuals experienced in basic and applied studies of age-related neurodegeneration. In all cases, the main criteria for successful candidates is dedication and interest in aging and neurodegeneration research and the highest level of academic achievement in their previous training. Students are required to participate in special neurodegeneration courses, seminars, and symposia. Close monitoring of student progress and career advising provide an effective structure for the entire training process. The purpose of the Program is to create a framework within which the best training of future researchers devoted to problems in aging and neurodegeneration can take place, and the already extensive collaborative interactions among the Program faculty can be propagated at all levels, from student to Professor.